The present invention relates to a process for the manufacture of coated articles wherein the coating comprises a polymer having desirable characteristics regarding adherence to the substrate, durability, hydrophilicity, wettability, biocompatibility and permeability. More particular, the present invention relates to a process for the modification of the surface of an article, such as a biomedical material or article, especially a contact lens including an extended-wear contact lens wherein the articles are at least partly coated with a polymer having a xe2x80x9cbottle-brushxe2x80x9d type structure composed of tethered xe2x80x9chairyxe2x80x9d chains.
A variety of different types of processes for preparing polymeric coatings on a substrate have been disclosed in the prior art. For example, U.S. Pat. No. 5,527,925 describes functionalized photoinitiators and also organic substrates such as contact lenses containing said photoinitiators covalently bound to their surface. In one embodiment of said disclosure, the so modified surface of the contact lens is further coated with a photopolymerizable ethylenically unsaturated monomer which is then polymerized by irradiation thus forming a novel substrate surface. With this method, however, it is not always possible to obtain the desired coating characteristics, for example wettability characteristics which are necessary for the surface of biomedical devices including contact lenses. In particular, the ability of the known materials to attract and stabilize a continuous layer of an aqueous solution, e.g. human body fluids such as tears or mucus layers, for a prolonged period of time which is an important feature for many biomedical applications is not yet satisfactory.
Surprisingly, it now has been found that articles, particularly biomedical devices such as contact lenses, with an improved wettability, water-retention ability and biocompatibility are obtained by first of all providing a monofunctional hydrophilic telomer having a bottle-brush type structure and then attaching the telomer to the material surface, for example, by reaction of its functional group with co-reactive groups being present on the material surface.
The present invention therefore in one aspect relates to a process for coating a material surface, comprising the steps of:
(a) providing a hydrophilic telomer of formula
(oligomer)-Txe2x80x83xe2x80x83(1),
xe2x80x83wherein
T is hydroxy, epoxy, amino, C1-C6-alkylamino, carboxy or a suitable carboxy derivative, for example a carboxylic acid ester or an acid halide, and (oligomer) is the radical of a telomer of formula
-(Alk)-S"Brketopenst"Z "Brketclosest"a"Brketopenst"Z "Brketclosest"bQxe2x80x83xe2x80x83(2),
xe2x80x83wherein
(Alk) is C2-C12-alkylene which may be interrupted by xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94,
Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator,
a and b are each independently of another an integer from 0 to 350, wherein the total of (a+b) is an integer from 2 to 350,
and Z and Zxe2x80x2 are each independently of the other a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer by replacing the vinylic double bond by a single bond, which radical carries a hydrophilic side chain having a weight average molecular weight of xe2x89xa7200; and
(b) covalently binding the hydrophilic telomer to the material surface.
The following meanings and preferences apply to the variables contained in the definition of the hydrophilic telomer of formula (1):
T as carboxy derivative is for example a radical xe2x80x94C(O)OC1-C4-alkyl or xe2x80x94C(O)Cl. T is preferably hydroxy, amino or carboxy, more preferably amino or carboxy and in particular amino.
(Alk) is preferably C2-C8-alkylene, more preferably C2-C6-alkylene, even more preferably C2-C4-alkylene and particularly preferably 1,2-ethylene. The alkylene radical (alk) may be branched or preferably linear alkylene.
Q is for example hydrogen.
The total of (a+b) is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 5 to 50. In a preferred embodiment of the invention b is 0 and a is an integer from 2 to 350, preferably from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75, and particularly preferably from 5 to 50.
A suitable 1,2-ethylene radical Z or Zxe2x80x2 is, for example, a radical of formula 
wherein
R1 is hydrogen or C1-C6-alkyl or a radical xe2x80x94COORxe2x80x2;
R, Rxe2x80x2 and R2 are each independently of the other hydrogen or C1-C6-alkyl; and
R3 is, for example, a non-ionic substituent selected from the group consisting of a radical xe2x80x94COOY10, wherein Y10 is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)yxe2x80x94E, E is hydrogen or C1-C6-alkyl and y is an integer from 3 to 24, or Y10 is a radical xe2x80x94C2-C6-alkyl-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide or is a radical xe2x80x94Oxe2x80x94(CH2CH2O)yxe2x80x94E wherein E and y are each as defined above; and a radical xe2x80x94CONY11Y12, wherein Y11 is hydrogen or unsubstituted or, for example, hydroxy-substituted C1-C24-alkyl, and Y12 is C1-C12-alkyl which is substituted by a radical xe2x80x94Oxe2x80x94(CH2CH2O)yxe2x80x94E and wherein E and y are as defined above; and a zwitter-ionic substituent of formula
xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY13)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(CH2)2xe2x80x94N(CH3)3+,
wherein Y13 is the acyl radical of a higher fatty acid; or
R3 is a radical of formula
xe2x80x94A-(oligomer1)xe2x80x83xe2x80x83(4),
wherein A is a direct bond or is a radical of formula
xe2x80x94C(O)xe2x80x94(A1)nxe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(5a) or
xe2x80x94(A2)mxe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(5b); or
xe2x80x94(A2)mxe2x80x94Xxe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(5c); or
xe2x80x94C(O)xe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(5d); or
xe2x80x94C(O)xe2x80x94X1xe2x80x94(alk*)Xxe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(5e); or
A and R1, together with the adjacent double bond, are a radical of formula 
A1 is xe2x80x94Oxe2x80x94C2-C12-alkylene which is unsubstituted or substituted by hydroxy, or is xe2x80x94Oxe2x80x94C2-C12-alkylene-NHxe2x80x94C(O)xe2x80x94 or xe2x80x94Oxe2x80x94C2-C12-alkylene-Oxe2x80x94C(O)xe2x80x94NHxe2x80x94R33xe2x80x94NHxe2x80x94C(O)xe2x80x94, wherein R33 is linear or branched C1-C18-alkylene or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, C7-C18-aralkylene, C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene, C3-C8-cycloalkylene, C3-C8-cycloalkylene-C1-C6-alkylene, C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C1-C6-alkylene-C3-C8-cycloalkylene-C1-C6-alkylene;
A2 is C1-C8-alkylene; phenylene or benzylene;
m and n are each independently of the other the number 0 or 1;
X, X1 and Xxe2x80x2 are each independently of the other a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NRxe2x80x3, wherein Rxe2x80x3 is hydrogen or C1-C6-alkyl;
(alk*) is C2-C12-alkylene;
and (oligomer1) is
(i) the radical of a telomer of formula
-(alk)-S"Brketopenst"B"Brketclosest"p"Brketopenst"Bxe2x80x2"Brketclosest"qQ1xe2x80x83xe2x80x83(6a),
xe2x80x83wherein
(alk) is C2-C12-alkylene,
Q1 is a monovalent group that is suitable to act as a polymerization chain-reaction terminator,
p and q are each independently of another an integer from 0 to 350, wherein the total of (p+q) is an integer from 2 to 350,
and B and Bxe2x80x2 are each independently of the other a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer by replacing the vinylic double bond by a single bond, at least one of the radicals B and Bxe2x80x2 being substituted by a hydrophilic substituent; or
(ii) the radical of an oligomer of the formula 
xe2x80x83wherein R19 is hydrogen or unsubstituted or hydroxy-substituted C1-C12-alkyl, u is an integer from 2 to 250 and Qxe2x80x2 is a radical of a polymerization initiator; or
(iii) the radical of formula 
xe2x80x83wherein X2 is xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94 or xe2x80x94NC1-C6-alkyl- and R19 and u are as defined above, or
(iv) the radical of an oligomer of formula 
xe2x80x83wherein R20 and R20xe2x80x2 are each independently C1-C4-alkyl, Anxe2x88x92 is an anion, v is an integer from 2 to 250, and Qxe2x80x3 is a monovalent group that is suitable to act as a polymerization chain-reaction terminator; or
(v) the radical of an oligopeptide of formula
xe2x80x94(CHR21xe2x80x94C(O)xe2x80x94NH)txe2x80x94CHR21xe2x80x94COOHxe2x80x83xe2x80x83(6d)
or
xe2x80x94CHR21xe2x80x94(NHxe2x80x94C(O)xe2x80x94CHR21)txe2x80x94NH2xe2x80x83xe2x80x83(6dxe2x80x2),
xe2x80x83wherein R21 is hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, carboxy, carbamoyl, amino, phenyl, o-, m- or p-hydroxyphenyl, imidazolyl, indolyl or a radical xe2x80x94NHxe2x80x94C(xe2x95x90NH)xe2x80x94NH2 and t is an integer from 2 to 250, or the radical of an oligopeptide based on proline or hydroxyproline; or
(vi) the radical of a polyalkylene oxide of formula
-(alk**-O)zxe2x80x94[CH2xe2x80x94CH2xe2x80x94O]rxe2x80x94[CH2xe2x80x94CH(CH3)xe2x80x94O]sxe2x80x94R34xe2x80x83xe2x80x83(6e),
xe2x80x83wherein R34 is hydrogen or C1-C24-alkyl, (alk**) is C2-C4-alkylene, z is 0 or 1, r and s are each independently an integer from 0 to 250 and the total of (r+s) is from 2 to 250; or
(vii) the radical of an oligosaccharide; subject to the provisos that
A is not a direct bond if (oligomer) is a radical of formula (6a);
A is a radical of formula (5a), (5b) or (5d) or A and R1, together with the adjacent double bond, are a radical of formula (5f) if (oligomer) is a radical of formula (6b), (6c), (6d) or (6e) or is the radical of an oligosaccharide;
A is a direct bond if (oligomer) is a radical of formula (6bxe2x80x2); and
A is a radical of formula (5c) or (5e) if (oligomer) is a radical of formula (6dxe2x80x2).
The following preferences apply to the variables contained in the definition of the radicals of formula (3):
R is preferably hydrogen or methyl, in particular hydrogen.
Rxe2x80x2 is preferably hydrogen or C1-C4-alkyl, more preferably hydrogen or C1-C2-alkyl and particularly preferably hydrogen.
R1 is preferably hydrogen, methyl or carboxyl, and particularly preferably hydrogen.
R2 is preferably hydrogen or methyl.
One group of suitable radicals R3 are those wherein R3 is a radical xe2x80x94COOY10, xe2x80x94CONY11Y12 or xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY13)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(CH2)2xe2x80x94N(CH3)3+, wherein Y10, Y11, Y12 and Y13 are each as defined above. E is preferably hydrogen or C1-C2-alkyl, y is preferably an integer from 3 to 16, more preferably from 4 to 12, and in particular from 5 to 10. Examples of suitable saccharide substituents xe2x80x94Oxe2x80x94G of the alkyl radical Y10 that is substituted by xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G are the radical of a mono- or disaccharide, for example glucose, acetyl glucose, methyl glucose, glucosamine, N-acetyl glucosamine, glucono lactone, mannose, galactose, galactosamine, N-acetyl galactosamine, fructose, maltose, lactose, fucose, saccharose or trehalose, the radical of an anhydrosaccharide such as levoglucosan, the radical of a glucosid such as octylglucosid, the radical of a sugar alcohol such as sorbitol, the radical of a sugar acid derivative such as lactobionic acid amide, or the radical of an oligosaccharide with a maximum of 8 sugar units, for example fragments of a cyclodextrin, starch, chitosan, maltotriose or maltohexaose. The saccharide radical xe2x80x94Oxe2x80x94G is preferably the radical of a mono- or disaccharide or the radical of a cyclodextrin fragment with a maximum of 8 sugar units. Particular preferred saccharide radicals xe2x80x94Oxe2x80x94G are the radical of trehalose or the radical of a cyclodextrin fragment. Y11 is preferably hydrogen.
A preferred radical Z or Zxe2x80x2 according to the invention is, for example, of the formula 
wherein for R, R1, R2 and Y10 each the above given meanings and preferences apply. A particular preferred radical Z or Zxe2x80x2 corresponds to the above formula (3xe2x80x2), wherein R and R1 are each hydrogen, R2 is hydrogen or methyl, and Y10 is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)4-12xe2x80x94E or xe2x80x94CH2CH2xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a mono- or disaccharide or the radical of an oligosaccharide and E is hydrogen or C1-C2-alkyl.
According to a further embodiment of the invention R3 is a radical of the above formula (4) wherein the above-given meanings and the preferences given below apply.
X is preferably a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94. X is particularly preferably the group xe2x80x94NHxe2x80x94 if (oligomer1) is a radical of formula (6a); (6c) or (6d), and is particularly preferably the group xe2x80x94Oxe2x80x94 if (oligomer1) is a radical of formula (6b) or (6e) or is the radical of an oligosaccharide. Xxe2x80x2 is preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 and more preferably xe2x80x94NHxe2x80x94. X1 is preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94.
R33 as alkylene is preferably a linear or branched C3-C14alkylene radical, more preferably a linear or branched C4-C12alkylene radical and most preferably a linear or branched C6-C10-alkylene radical. Some preferred alkylene radicals are 1,4-butylene, 2,2-dimethyl-1,4-butylene, 1,5-pentylene, 2,2-dimethyl-1,5-pentylene, 1,6-hexylene, 2,2,3- or 2,2,4-trimethyl-1,5-pentylene, 2,2-dimethyl-1,6-hexylene, 2,2,3- or 2,2,4- or 2,2,5-trimethyl-1,6-hexylene, 2,2-dimethyl-1,7-heptylene, 2,2,3- or 2,2,4- or 2,2,5- or 2,2,6-trimethyl-1,7-heptylene, 1,8-octylene, 2,2-dimethyl-1,8-octylene and 2,2,3- or 2,2,4- or 2,2,5- or 2,2,6- or 2,2,7-trimethyl-1,8-octylene.
When R33 is arylene, it is, for example, naphthylene or especially phenylene, each of which may be substituted, for example, by C1-C4-alkyl or by C1-C4-alkoxy. Preferably, R33 as arylene is 1,3- or 1,4-phenylene that is unsubstituted or substituted by C1-C4-alkyl or by C1-C4-alkoxy in the ortho-position to at least one linkage site. Examples of substituted arylene are 1-methyl-2,4-phenylene, 1,5-dimethyl-2,4-phenylene, 1-methoxy-2,4-phenylene and 1-methyl-2,7-naphthylene.
R33 as aralkylene is preferably naphthylalkylene and most preferably phenylalkylene. The alkylene group in aralkylene contains preferably from 1 to 12, more preferably from 1 to 6 and most preferably from 1 to 4 carbon atoms. Most preferably, the alkylene group in aralkylene is methylene or ethylene. Some examples are 1,3- or 1,4-benzylene, naphth-2-yl-7-methylene, 6-methyl-1,3- or -1,4-benzylene and 6-methoxy-1,3- or -1,4-benzylene.
When R33 is cycloalkylene, it is preferably C5-C6-cycloalkylene and most preferably cyclohexylene that is unsubstituted or substituted by methyl. Some examples are 1,3-cyclobutylene, 1,3-cyclopentylene, 1,3- or 1,4-cyclohexylene, 1,3- or 1,4-cycloheptylene, 1,3- or 1,4- or 1,5-cyclooctylene, 4-methyl-1,3-cyclopentylene, 4-methyl-1,3-cyclohexylene, 4,4-dimethyl-1,3-cyclohexylene, 3-methyl- or 3,3-dimethyl-1,4-cyclohexylene, 3,5-dimethyl-1,3-cyclohexylene and 2,4-dimethyl-1,4-cyclohexylene.
When R33 is cycloalkylene-alkylene, it is preferably cyclopentylene-C1-C4-alkylene and especially cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group cycloalkylene-alkylene is cyclohexylene-ethylene and, most preferably, cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups. Some examples are cyclopent-1-yl-3-methylene, 3-methyl-cyclopent-1-yl-3-methylene, 3,4-dimethyl-cyclopent-1-yl-3-methylene, 3,4,4-trimethyl-cyclopent-1-yl-3-methylene, cyclohex-1-yl-3- or -4-methylene, 3- or 4- or 5-methyl-cyclohex-1-yl-3- or -4-methylene, 3,4- or 3,5-dimethyl-cyclohex-1-yl-3- or -4-methylene and 3,4,5- or 3,4,4- or 3,5,5-trimethyl-cyclohex-1-yl-3- or -4-methylene.
When R33 is alkylene-cycloalkylene-alkylene, it is preferably C1-C4-alkylene-cyclopentylene-C1-C4-alkylene and especially C1-C4-alkylene-cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group alkylene-cycloalkylene-alkylene is ethylene-cyclohexylene-ethylene and, most preferably, is methylene-cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups. Some examples are cyclopentane-1,3-dimethylene, 3-methyl-cyclopentane-1,3-dimethylene, 3,4-dimethyl-cyclopentane-1,3-dimethylene, 3,4,4-trimethyl-cyclopentane-1,3-dimethylene, cyclohexane-1,3- or -1,4-dimethylene, 3- or 4- or 5-methyl-cyclohexane-1,3- or -1,4-dimethylene, 3,4- or 3,5-dimethyl-cyclohexane-1,3- or -1,4-dimethylene, 3,4,5- or 3,4,4- or 3,5,5-trimethyl-cyclohexane-1,3- or -1,4-dimethylene.
R33 as C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene is preferably C5-C6-cycloalkylene-methylene-C5-C6-cycloalkylene or phenylene-methylene-phenylene, each of which may be unsubstituted or substituted in the cycloalkyl or phenyl ring by one or more methyl groups.
The radical R33 has a symmetrical or, preferably, an asymmetrical structure. A preferred group of radicals R11, comprises those, wherein R33 is linear or branched C6-C10alkylene; cyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene each unsubstituted or substituted in the cyclohexyl moiety by from 1 to 3 methyl groups; or phenylene or phenylene-methylene-phenylene each unsubstituted or substituted in the phenyl moiety by methyl. The bivalent radical R33 is derived preferably from a diisocyanate and most preferably from a diisocyanate selected from the group isophorone diisocyanate (IPDI), toluylene-2,4-diisocyanate (TDI), 4,4xe2x80x2-methylenebis(cyclohexyl isocyanate), 1,6diisocyanato-2,2,4-trimethyl-n-hexane (TMDI), methylenebis(phenyl isocyanate), methylenebis(cyclohexyl-4-isocyanate) and hexamethylene diisocyanate (HMDI).
Preferred meanings of A1 are unsubstituted or hydroxy-substituted xe2x80x94Oxe2x80x94C2-C8-alkylene or a radical xe2x80x94Oxe2x80x94C2-C6-alkylene-NHxe2x80x94C(O)xe2x80x94 and particularly xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or a radical xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94NHxe2x80x94C(O)xe2x80x94. A particularly preferred meaning of Al is the radical xe2x80x94Oxe2x80x94(CH2)2xe2x80x94NHxe2x80x94C(O)xe2x80x94.
A2 is preferably C1-C6-alkylene, phenylene or benzylene, more preferably C1-C4-alkylene and even more preferably C1-C2-alkylene. n is an integer of 0 or preferably 1. m is preferably an integer of 1. In case that (oligomer1) is a radical of formula (6a), (6b), (6c), (6d) or (6e) or is the radical of an oligosaccharide, A preferably denotes a radical of formula (5a) or (5b) and particularly preferably a radical of formula (5a), wherein the above given meanings and preferences apply for the variables contained therein.
A preferred group of radicals Z or Zxe2x80x2 according to the invention comprises radicals of the above formula (3), wherein R2 is hydrogen or methyl, R1 is hydrogen, methyl or carboxyl, R is hydrogen, and R3 is a radical of the above formula (4) wherein A is a radical of the formula (5a) or (5b) and (oligomer1) is a radical of formula (6a), (6b), (6c), (6d) or (6e) or is the radical of an oligosaccharide. An even more preferred group of radicals Z or Zxe2x80x2 comprises radicals of the above formula (3), wherein R2 is hydrogen or methyl, R and R1 are each hydrogen, and R3 is a radical of the formula (4), wherein A is a radical of the formula (5a) and (oligomer1) is a radical of formula (6a). A further group of preferred radicals Z or Zxe2x80x2 comprises radicals of formula (3), wherein R2 is hydrogen or methyl, R and R1 are each hydrogen, and R3 is a radical of the formula (4), wherein A is a radical of formula (5e) above and (oligomer1) is a radical of formula (6a).
(alk) and (alk*) are each independently preferably C2-C8-alkylene, more preferably C2-C6alkylene, even more preferably C2-C4-alkylene and particularly preferably 1,2-ethylene. The alkylene radicals (alk) and (alk*) may be branched or preferably linear alkylene radicals.
Q is for example hydrogen.
The total of (p+q) is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50. In a preferred embodiment of the invention q is 0 and p is an integer from 2 to 250, preferably from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50.
Suitable hydrophilic substituents of the radicals B or Bxe2x80x2 may be non-ionic, anionic, cationic or zwitterionic substituents. Accordingly, the telomer chain of formula (5a) that contains monomer units B and/or Bxe2x80x2 may be a charged chain containing anionic, cationic and/or zwitterionic groups or may be an uncharged chain. In addition, the telomer chain may comprise a copolymeric mixture of uncharged and charged units. The distribution of the charges within the telomer, if present, may be random or blockwise.
In one preferred embodiment of the invention, the telomer radical of formula (6a) is composed solely of non-ionic monomer units B and/or Bxe2x80x2. In another preferred embodiment of the invention, the telomer radical of formula (6a) is composed solely of ionic monomer units B and/or Bxe2x80x2, for example solely of cationic monomer units or solely of anionic monomer units. Still another preferred embodiment of the invention is directed to telomer radicals of formula (6a) comprising nonionic units B and ionic units Bxe2x80x2.
Suitable non-ionic substituents of B or Bxe2x80x2 include for example a radical C1-C6-alkyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94OH, C1-C4-alkoxy and xe2x80x94NR23R23xe2x80x2, wherein R23 and R23xe2x80x2 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl; phenyl which is substituted by hydroxy, C1-C4-alkoxy or xe2x80x94NR23R23xe2x80x2, wherein R23 and R23xe2x80x2 are as defined above; a radical xe2x80x94COOY, wherein Y is C1-C24-alkyl which is unsubstituted or substituted, for example, by hydroxy, C1-C4-alkoxy, xe2x80x94Oxe2x80x94Si(CH3)3, xe2x80x94NR23R23xe2x80x2 wherein R23 and R23xe2x80x2 are as defined above, a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E wherein E is hydrogen or C1-C6-alkyl, or a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide with 1 to 8 sugar units or is a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E, wherein E is as defined above, or Y is C5-C8-cycloalkyl which is unsubstituted or substituted by C1-C4-alkyl or C1-C4-alkoxy, or is unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted phenyl or C7-C12-aralkyl; xe2x80x94CONY1Y2 wherein Y1 and Y2 are each independently hydrogen, C1-C12-alkyl, which is unsubstituted or substituted for example by hydroxy, C1-C4-alkoxy or a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E wherein E is as defined above, or Y1 and Y2 together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen; or C1-C12-alkyl which is unsubstituted or substituted by xe2x80x94NR23R23xe2x80x2; or is a radical xe2x80x94C(O)xe2x80x94C1-C4-alkyl; and wherein R23 and R23xe2x80x2 are as defined above; or a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom.
Suitable anionic substituents of B or Bxe2x80x2 include for example C1-C6-alkyl which is substituted by xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 and xe2x80x94COOH; phenyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94SO3H, xe2x80x94COOH, xe2x80x94OH and xe2x80x94CH2xe2x80x94SO3H; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C1-C24-alkyl which is substituted for example by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of an anionic carbohydrate; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C24-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, or xe2x80x94OPO3H2 and Y6 independently has the meaning of Y5 or is hydrogen or C1-C12-alkyl; or xe2x80x94SO3H; or a salt thereof, for example a sodium, potassium, ammonium or the like salt thereof.
Suitable cationic substituents of B or Bxe2x80x2 include C1-C12-alkyl which is substituted by a radical xe2x80x94NR23R23xe2x80x2R23xe2x80x3+Anxe2x88x92, wherein R23, R23xe2x80x3 and R23xe2x80x3 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl, and Anxe2x88x92 is an anion; or a radical xe2x80x94C(O)OY7, wherein Y7 is C1-C24-alkyl which is substituted by xe2x80x94NR23R23xe2x80x2R23xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted for example by hydroxy, wherein R23 R23xe2x80x2, R23xe2x80x3 and Anxe2x88x92 are as defined above.
Suitable zwitterionic substituents of B or Bxe2x80x2 include a radical xe2x80x94R24xe2x80x94Zw, wherein R24 is a direct bond or a functional group, for example a carbonyl, carbonate, amide, ester, dicarboanhydride, dicarboimide, urea or urethane group; and Zw is an aliphatic moiety comprising one anionic and one cationic group each.
The following preferences apply to the hydrophilic substituents of B and Bxe2x80x2:
(i) Non-ionic Substituents
Preferred alkyl substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR23R23xe2x80x2, wherein R23 and R23xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl, preferably hydrogen, methyl or ethyl and particularly preferably hydrogen or methyl, for example xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94N(CH3)2. Preferred phenyl substituents of B or Bxe2x80x2 are phenyl which is substituted by xe2x80x94NH2 or N(C1-C2-alkyl)2, for example o-, m- or p-aminophenyl. In case that the hydrophilic substituent of B or Bxe2x80x2 is a radical xe2x80x94COOY, Y as optionally substituted alkyl is preferably C1-C12-alkyl, more preferably C1-C6-alkyl, even more preferably C1-C4-alkyl and particularly preferably C1-C2-alkyl, each of which being unsubstituted or substituted as mentioned above. In case that the alkyl radical Y is substituted by xe2x80x94NR23R23xe2x80x2, the above-given meanings and preferences apply for R23 and R23xe2x80x2. Examples of suitable saccharide substituents xe2x80x94Oxe2x80x94G of the alkyl radical Y that is substituted by xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G are the radical of a mono- or disaccharide, for example glucose, acetyl glucose, methyl glucose, glucosamine, N-acetyl glucosamine, glucono lactone, mannose, galactose, galactosamine, N-acetyl galactosamine, fructose, maltose, lactose, fucose, saccharose or trehalose, the radical of an anhydrosaccharide such as levoglucosan, the radical of a glucosid such as octylglucosid, the radical of a sugar alcohol such as sorbitol, the radical of a sugar acid derivative such as lactobionic acid amide, or the radical of an oligosaccharide with a maximum of 8 sugar units, for example fragments of a cyclodextrin, starch, chitosan, maltotriose or maltohexaose. The radical xe2x80x94Oxe2x80x94G preferably denotes the radical of a mono- or disaccharide or the radical of a cyclodextrin fragment with a maximum of 8 sugar units. Particular preferred saccharide radicals xe2x80x94Oxe2x80x94G are the radical of trehalose or the radical of a cyclodextrin fragment. In case that the alkyl radical Y is substituted by a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E or xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94E, the number of (CH2CH2O) units is preferably from 1 to 12 in each case and more preferably from 2 to 8. E is preferably hydrogen or C1-C2-alkyl. Y as C5-C8-cycloalkyl is for example cyclopentyl or preferably cyclohexyl, each of which being unsubstituted or substituted for example by 1 to 3 C1-C2-alkyl groups.Y as C7-C12-aralkyl is for example benzyl.
Preferred nonionic radicals xe2x80x94COOY are those wherein Y is C1-C6-alkyl; or C2-C6-alkyl which is substituted by one or two substituents selected from the group consisting of hydroxy;; C1-C2-alkoxy; xe2x80x94Oxe2x80x94Si(CH3)3; and xe2x80x94NR23R23xe2x80x2 wherein R23 and R23xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl; or Y is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12xe2x80x94E wherein E is hydrogen or C1-C2-alkyl; or is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
More preferred non-ionic radicals xe2x80x94COOY are those wherein Y is C1-C4-alkyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR23R23xe2x80x2 wherein R23 and R23xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl; or a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12xe2x80x94E wherein E is hydrogen or C1-C2-alkyl; or is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
Particularly preferred radicals xe2x80x94COOY comprise those wherein Y is C1-C2-alkyl, particularly methyl; or C2-C3-alkyl, which is unsubstituted or substituted by hydroxy or N,N-di-C1-C2-alkylamino, or is a radical xe2x80x94C2-C3-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose or the radical of a cyclodextrin fragment with a maximum of 8 sugar units.
Preferred non-ionic substituents xe2x80x94C(O)xe2x80x94NY1Y2 of B or Bxe2x80x2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom. Even more preferred meanings of Y1 and Y2, independently of each other, are hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring. Particularly preferred non-ionic radicals xe2x80x94C(O)xe2x80x94NY1Y2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C2-alkyl; or Y1 and Y2 together with the adjacent N-atom form a morpholino ring.
Preferred non-ionic substituents xe2x80x94OY3 of B or Bxe2x80x2 are those wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl. Y3 is particularly preferred hydrogen or acetyl.
Preferred non-ionic heterocyclic substituents of B or Bxe2x80x2 are a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N- or O- heteroatom, or is a 5 to 7-membered lactame. Examples of such heterocyclic radicals are N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methyl pyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl, N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl or 4-N-methylpiperazin-1-yl, particularly N-morpholinyl or N-pyrrolidonyl.
A group of preferred non-ionic substituents of B or Bxe2x80x2 comprises C1-C2-alkyl, which is unsubstituted or substituted by xe2x80x94OH or xe2x80x94NR23R23xe2x80x2, wherein R23 and R23xe2x80x2 are each independently of the other hydrogen or C1-C2-alkyl; a radical xe2x80x94COOY wherein Y is C1-C4-alkyl; C2-C4-alkyl which is substituted by xe2x80x94OH, xe2x80x94NR23R23xe2x80x2 wherein R23 and R23xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl, or Y is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide; a radical xe2x80x94C(O)xe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further Nxe2x80x94 or O-atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl; or a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N-, O- or S-heteroatom, or a 5 to 7-membered lactame.
A group of more preferred non-ionic substituents of B or Bxe2x80x2 comprises a radical xe2x80x94COOY, wherein Y is C1-C2-alkyl, C2-C3-alkyl, which is substituted by hydroxy, amino or N,N-di-C1-C2-alkylamino, or is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose or a cyclodextrin fragment with a maximum of 8 sugar units; a radical xe2x80x94COxe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring; or a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl, N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.
A particularly preferred group of non-ionic substituents of B or Bxe2x80x2 comprises the radicals xe2x80x94CONH2, xe2x80x94CON(CH3)2, 
xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, xe2x80x94COOxe2x80x94(CH2)2xe2x80x94N(CH3)2, and xe2x80x94COO(CH2)2-4xe2x80x94NHC(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose.
(ii) Anionic Substituents
Preferred anionic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94SO3H and xe2x80x94OPO3H2, for example xe2x80x94CH2xe2x80x94SO3H; phenyl which is substituted by xe2x80x94SO3H or sulfomethyl, for example o-, m- or p-sulfophenyl or o-, m- or p-sulfomethylphenyl; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C2-C6-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2, or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of lactobionic acid, hyaluronic acid or sialic acid, in particular C2-C4-alkyl which is substituted by xe2x80x94SO3H or xe2x80x94OSO3H; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C6-alkyl substituted by sulfo, in particular C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, for example the radical xe2x80x94C(O)xe2x80x94NHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94SO3H; or xe2x80x94SO3H; or a suitable salt thereof. Particular preferred anionic substituents of B or Bxe2x80x2 are xe2x80x94COOH, xe2x80x94SO3H, o-, m- or p-sulfophenyl, o-, m- or p-sulfomethylphenyl or a radical xe2x80x94CONY5Y6 wherein Y5 is C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen.
(iii) Cationic Substituents
Preferred cationic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is in each case substituted by xe2x80x94NR23R23xe2x80x2R23xe2x80x3+Anxe2x88x92; or a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C6-alkyl in particular C2-C4-alkyl, which is in each case substituted by xe2x80x94NR23R23xe2x80x2R23xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted by hydroxy. R23, R23xe2x80x2 and R23xe2x80x3 are each independently of another preferably hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. Examples of suitable anions Anxe2x88x92 are Halxe2x88x92, wherein Hal is halogen, for example Brxe2x88x92, Fxe2x88x92, Jxe2x88x92 or particularly Clxe2x88x92, furthermore HCO3xe2x88x92, CO32xe2x88x92, H2PO3xe2x88x92, HPO32xe2x88x92, PO33xe2x88x92, HSO4xe2x88x92 , SO42xe2x88x92 or the radical of an organic acid such as OCOCH3xe2x88x92 and the like. A particularly preferred cationic substituent of B or Bxe2x80x2 is a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C4-alkyl, which is substituted by xe2x80x94N(C1-C2-alkyl)3+Anxe2x88x92 and is further substituted by hydroxy, and Anxe2x88x92 is an anion, for example the radical xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94N(CH3)3+Anxe2x88x92.
(iv) Zwitterionic Substituents xe2x80x94R24xe2x80x94Zw
R24 is a preferably a carbonyl, ester or amide functional group and more preferably an ester group xe2x80x94C(O)xe2x80x94Oxe2x80x94. Suitable anionic groups of the moiety Zw are for example xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92, xe2x80x94OPO3Hxe2x88x92 or bivalent xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94 or xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94Oxe2x80x94, preferably a group xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 or a bivalent group xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94, and in particular a group xe2x80x94SO3xe2x88x92. Suitable cationic groups of the moiety Zw are for example a group xe2x80x94NR23R23xe2x80x2R23xe2x80x3+ or a bivalent group xe2x80x94NR23R23xe2x80x2+xe2x80x94, wherein R23, R23xe2x80x2 and R23xe2x80x3 are as defined above, and are each independently of the other, preferably hydrogen or C1-C6-alkyl, preferably hydrogen or C1-C4-alkyl and most preferably each methyl or ethyl.
The moiety Zw is for example C2-C30-alkyl, preferably C2-C12-alkyl, and more preferably C3-C8-alkyl, which is in each case uninterrupted or interrupted by xe2x80x94Oxe2x80x94 and substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and, in addition, is further unsubstituted or substituted by a radical xe2x80x94OY8, wherein Y8 is hydrogen or the acyl radical of a carboxylic acid.
Y8 is preferably hydrogen or the acyl radical of a higher fatty acid.
Zw is preferably C2-C12-alkyl and even more preferably C3-C8-alkyl which is substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and in addition may be further substituted by a radical xe2x80x94OY8.
A preferred group of zwitter-ionic substituents xe2x80x94R24xe2x80x94Zw corresponds to the formula
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R23)2+xe2x80x94(alkxe2x80x2)xe2x80x94Anxe2x88x92
or
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x3)xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(O)0-1xe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R23)3+
wherein R23 is hydrogen or C1-C6-alkyl; Anxe2x88x92 is an anionic group xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92 or xe2x80x94OPO3Hxe2x88x92, preferably xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 and most preferably xe2x80x94SO3xe2x88x92, alkxe2x80x2 is C1-C12-alkylene, (alkxe2x80x3) is C2-C24-alkylene which is unsubstituted or substituted by a radical xe2x80x94OY8, Y8 is hydrogen or the acyl radical of a carboxylic acid, and (alkxe2x80x2xe2x80x3) is C2-C8-alkylene.
(alkxe2x80x2) is preferably C2-C8-alkylene, more preferably C2-C6-alkylene and most preferably C2-C4-alkylene. (alkxe2x80x3) is preferably C2-C12-alkylene, more preferably C2-C6-alkylene and particularly preferably C2-C3-alkylene which is in each case unsubstituted or substituted by hydroxy or by a radical xe2x80x94OY8. (alkxe2x80x2xe2x80x3) is preferably C2-C4-alkylene and more preferably C2-C3-alkylene. R9 is hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. A preferred zwitterionic substituent of B or Bxe2x80x2 is of formula
xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY8)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x80x94(CH2)2xe2x80x94N(CH3)3+,
wherein Y8 is hydrogen or the acyl radical of a higher fatty acid.
B denotes for example a radical of formula 
wherein R25 is hydrogen or C1-C4-alkyl, preferably hydrogen or methyl; R26 is a hydrophilic substituent, wherein the above given meanings and preferences apply; R27 is C1-C4-alkyl, phenyl or a radical xe2x80x94C(O)OY9, wherein Y9 is hydrogen or unsubstituted or hydroxy-substituted C1-C4-alkyl; and R28 is a radical xe2x80x94C(O)Y9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9xe2x80x2 independently has the meaning of Y9.
R27 is preferably C1-C2-alkyl, phenyl or a group xe2x80x94C(O)OY9. R28 is preferably a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each independently of the other hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl. Particularly preferred xe2x80x94CHR27xe2x80x94CHR28xe2x80x94 units according to the invention are those wherein R27 is methyl or a group xe2x80x94C(O)OY9 and R28 is a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl.
Bxe2x80x2 independently may have one of the meanings given above for B.
If (oligomer1) is a radical of formula (6a), the radical -(alk)-S-[B]p-[Bxe2x80x2]q-Q preferably denotes a radical of formula 
even more preferably of the formula 
wherein for (alk) R25, R26, Q1, p and q the above-given meanings and preferences apply, for R25xe2x80x2 independently the meanings and preferences given before for R25 apply, and for R26xe2x80x2 independently the meanings and preferences given before for R26 apply.
A preferred radical Z or Zxe2x80x2 is, for example a radical of formula 
wherein R2 is hydrogen or methyl, A1 is xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or a radical xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94NHxe2x80x94C(O)xe2x80x94, X is xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, (alk) is C2-C4-alkylene, Q1 is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p is an integer from 5 to 50, R25 and R25xe2x80x2 are each independently of the other hydrogen or methyl, and for R26 and R26xe2x80x2 each independently the above given meanings and preferences apply.
A particularly preferred radical Z or Zxe2x80x2 is, for example, of the formula 
wherein for R2, R25, R26, Q1, (alk) and p the above-given meanings and preferences apply. A particularly preferred group of radicals of the above formula (3b) are those wherein R2 is hydrogen or methyl, (alk) is C2-C4-alkylene, R25 is hydrogen or methyl, p is an integer of 5 to 50, Q is as defined before, and for R26 the above given meanings and preferences apply; in particular R26 of this embodiment is a radical xe2x80x94CONH2, xe2x80x94CON(CH3)2 or 
If (oligomer1) is a radical (ii) of formula (6b), Qxe2x80x2 in formula (6b) is for example C1-C12-alkyl, phenyl or benzyl, preferably C1-C2-alkyl or benzyl and in particular methyl. R19 is preferably unsubstituted or hydroxy-substituted C1-C4-alkyl and in particular methyl, u is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 5 to 50.
If (oligomer1) is a radical of formula (6bxe2x80x2), the above given meanings and preferences apply for the variables R19 and u contained therein. X2 in formula (6bxe2x80x2) is preferably hydroxy or amino.
If (oligomer1) denotes a radical (iv) of formula (6c), R20 and R20xe2x80x2 are each preferably ethyl or in particular methyl; v is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 5 to 50; Qxe2x80x3 is for example hydrogen; and Anxe2x88x92 is as defined before.
If (oligomer1) denotes an oligopeptide radical (v) of formula (6d) or 6dxe2x80x2), R21 is for example hydrogen, methyl, hydroxymethyl, carboxymethyl, 1-hydroxyethyl, 2-carboxyethyl, isopropyl, n-, sec. or iso-butyl, 4-amino-n-butyl, benzyl, p-hydroxybenzyl, imidazolylmethyl, indolylmethyl or a radical xe2x80x94(CH2)3xe2x80x94NHxe2x80x94C(xe2x95x90NH)xe2x80x94NH2. t is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 5 to 50.
If (oligomer1) denotes a polyoxyalkylene radical (vi) of formula (6e), R34 is preferably hydrogen or C1-C18-alkyl, more preferably hydrogen or C1-C12-alkyl, even more preferably hydrogen, methyl or ethyl, and particularly preferably hydrogen or methyl. (alk**) is preferably a C2-C3-alkylene radical. z is preferably 0. r and s are each independently preferably an integer from 0 to 100 wherein the total of (r+s) is 5 to 100. r and s are each independently more preferably an integer from 0 to 50 wherein the total of (r+s) is 8 to 50. In a particularly preferred embodiment of the polyoxyalkylene radicals (oligomer), r is an integer from 8 to 50 and particularly 9 to 25, and s is 0.
(oligomer1) as the radical of an oligosaccharide (vii) may be, for example, a di- or polysaccharide including carbohydrate containing fragments from a biopolymer. Examples are the radical of a cyclodextrin, trehalose, cellobiose, maltotriose, maltohexaose, chitohexaose or a starch, hyaluronic acid, deacetylated hyaluronic acid, chitosan, agarose, chitin 50, amylose, glucan, heparin, xylan, pectin, galactan, glycosaminoglycan, mucin, dextran, aminated dextran, cellulose, hydroxyalkylcellulose or carboxyalkylcellulose oligomer, each of which with a molecular weight average weight of, for example, up to 25000, preferably up to 10000. Preferably the oligosaccharide according to (vii) is the radical of a cyclodextrin with a maximum of 8 sugar units.
Formulae (2), (3a), (6a), or (6e) are to be understood as a statistic description of the respective oligomeric radicals, that is to say, the orientation of the monomers and the sequence of the monomers (in case of copolymers) are not fixed in any way by said formulae. The arrangement of Z and Zxe2x80x2 in formula (2), the 1,2 ethylene units in formula (3a), B and Bxe2x80x2 in formula (6a) or of the ethyleneoxide and propyleneoxide units in formula (6e) thus in each case may be random or blockwise.
The weight average molecular weight of the hydrophilic side chains of the radicals Z or Zxe2x80x2 is for example xe2x89xa7200, preferably from 200 to 25000, more preferably from 300 to 12000, even more preferably from 300 to 8000, most preferably from 300 to 5000 and particularly preferably from 500 to 4000.
The hydrophilic telomers of formula (1) may be prepared, for example, according to PCT application WO 92/09639 by copolymerizing one or more hydrophilic ethylenically unsaturated monomers underlying the radicals Z and optionally Zxe2x80x2 in the presence of a functional chain transfer agent such as cysteamine hydrochloride, thioglycolic acid or the like. If desired, the group T then may be further modified in order to introduce an epoxy group or the like.
The ethylenically unsaturated monomers underlying the radicals Z or Zxe2x80x2 wherein R3 is a radical xe2x80x94COOY10 or xe2x80x94CONY10Y11 or the like are known or may be prepared according to methods that are known per se. For example, (meth)acryloylchloride is reacted with a polyethyleneoxide or a Jeffamine, or an isocyanatoalkyl(meth)acrylate is reacted with a polyethyleneoxide or a saccharide.
The ethylenically unsaturated monomers underlying the radicals Z or Zxe2x80x2 wherein R3 is a radical of formula (4) may be prepared, for example, by reacting a compound of formula 
wherein R, R1 and R2 each have the above-given meaning and A* is, for example, a group xe2x80x94C(O)xe2x80x94A**, wherein A** is halogen, particularly chlorine, an ester group an oxyalkylene radical comprising an epoxy group, for example the radical 
or is a radical xe2x80x94Oxe2x80x94C2-C12-alkylene-Nxe2x95x90Cxe2x95x90O; or A* is a radical xe2x80x94(A2)mxe2x80x94Nxe2x95x90Cxe2x95x90O, wherein A2 and m have the above-given meaning, with a compound of formula
HX-(oligomer1)xe2x80x83xe2x80x83(9),
wherein X has the above-given meaning.
The reactions of a compound of formula (8) having a carboxylic acid halide group, an epoxy group or an isocyanato group with an amino or hydroxy compound of formula (9) are well-known in the art and may be carried out as desribed in textbooks of organic chemistry. For example, the reaction of an isocyanato derivative of formula (8) with a compound of formula (9) may be carried out in an inert organic solvent such as an optionally halogenated hydrocarbon, for example petroleum ether, methylcyclohexane, toluene, chloroform, methylene chloride and the like, or an ether, for example diethyl ether, tetrahydrofurane, dioxane, or a more polar solvent such as DMSO, DMA, N-methylpyrrolidone or even a lower alcohol, at a temperature of from 0 to 100xc2x0 C., preferably from 0 to 50xc2x0 C. and particularly preferably at room temperature, optionally in the presence of a catalyst, for example a tertiary amine such as triethylamine or tri-n-butylamine, 1,4-diazabicyclooctane, or a tin compound such as dibutyltin dilaurate or tin dioctanoate. In addition, the reaction of an isocyanato derivative of formula (8) with a compound of formula (9) wherein xe2x80x94XH is an amino group also may be carried out in an aqueous solution in the absence of a catalyst. It is advantageous to carry out the above reactions under an inert atmosphere, for example under an nitrogen or argon atmosphere.
Moreover, the ethylenically unsaturated monomers underlying the radicals Z or Zxe2x80x2 wherein R3 is a radical of formula (4) and A is a radical of formula (5c) or (5e) may be obtained by reacting a compound of formula 
wherein R, R1, R2, A2, X, X1, (alk*) and m each have the above-given meaning, with a compound of formula
xe2x80x94X1xe2x80x2(O)Cxe2x80x94 (oligomer1)xe2x80x83xe2x80x83(11),
wherein (oligomer1) has the above-given meaning and X1xe2x80x2 is for example xe2x80x94OH or halogen, in particular chlorine, or together with xe2x80x94(O)Cxe2x80x94 forms a carboxy anhydride group, in a manner known per se.
The ethylenically unsaturated monomers underlying the radicals Z or Zxe2x80x2 wherein R3 is a radical of formula (4), A is a direct bond and (oligomer1) is a radical of formula (6cxe2x80x2) are known or may be prepared according to methods known in the art, for example as described in S. Kobayashi et al., Polymer Bulletin 13, p 447-451 (1985).
Likewise, the ethylenically unsaturated monomers of the formula 
wherein (alk*), Xxe2x80x2, X and (oligomer1) each have the above-given meaning, may be obtained in a manner known per se, for example, by reacting a compound of formula 
wherein (alk*) has the above-given meaning, with a compound of the above-given formula (6), or by reacting a compound of formula 
with a compound of the above formula (9) wherein (alk*) and X1 each have the above-given meaning.
The compounds of the formula (8), (9), (10a), (10b), (11), (12) and (12a) are known compounds which are commercially available or may be prepared according to known methods. For example, compounds of the formula (9) and (11) wherein (oligomer1) denotes a radical of formula (6a) may be prepared according to PCT application WO 92/09639 by copolymerizing one or more hydrophilic ethylenically unsaturated monomers in the presence of a functional chain transfer agent such as cysteamine hydrochloride, thioglycolic acid or the like.
Examples of materials that may be coated according to the process of the invention are quartz, ceramics, glasses, silicate minerals, silica gels, metals, metal oxides, carbon materials such as graphite or glassy carbon, natural or synthetic organic polymers, or laminates, composites or blends of said materials, in particular natural or synthetic organic polymers which are known in large number. Some examples of polymers are polyaddition and polycondensation polymers (polyurethanes, epoxy resins, polyethers, polyesters, polyamides and polyimides); vinyl polymers (polyacrylates, polymethacrylates, polystyrene, polyethylene and halogenated derivatives thereof, polyvinyl acetate and polyacrylonitrile); elastomers (silicones, polybutadiene and polyisoprene); or modified or unmodified biopolymers (collagen, cellulose, chitosan and the like).
A preferred group of materials to be coated are those being conventionally used for the manufacture of biomedical devices, e.g. contact lenses, in particular contact lenses for extended wear, which are not hydrophilic per se. Such materials are known to the skilled artisan and may comprise for example polysiloxanes, perfluoropolyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl (meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, or fluorinated polyolefines, such as fluorinated ethylene propylene, or tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-1,3-dioxol. Examples of suitable bulk materials are e.g. Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon, Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon or Teflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which are copolymers of about 63 to 73 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 37 to 27 mol % of tetrafluoroethylene, or of about 80 to 90 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 20 to 10 mol % of tetrafluoroethylene.
Another preferred group of materials to be coated are those being conventionally used for the manufacture of biomedical devices, e.g. contact lenses, which are hydrophilic per se, since reactive groups, e.g. carboxy, carbamoyl, sulfate, sulfonate, phosphate, amine, ammonium or hydroxy groups, are inherently present in the material and therefore also at the surface of a biomedical device manufactured therefrom. Such materials are known to the skilled artisan and comprise for example polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate (HEMA), polyvinyl pyrrolidone (PVP), polyacrylic acid, polymethacrylic acid, polyacrylamide, polydimethylacrylamide (DMA), polyvinyl alcohol or copolymers for example from two or more monomers from the group hydroxyethyl acrylate, hydroxyethyl methacrylate, N-vinyl pyrrolidone, acrylic acid, methacrylic acid, acrylamide, dimethyl acrylamide, vinyl alcohol and the like. Typical examples are e.g. Polymacon, Tefilcon, Methafilcon, Deltafilcon, Bufilcon, Phemfilcon, Ocufilcon, Focofilcon, Etafilcon, Hefilcon, Vifilcon, Tetrafilcon, Perfilcon, Droxifilcon, Dimefilcon, Isofilcon, Mafilcon, Nelfilcon or Atlafilcon.
Still another group of preferred materials to be coated are amphiphilic segmented copolymers comprising at least one hydrophobic segment and at least one hydrophilic segment which are linked through a bond or a bridge member. Examples are silicone hydrogels, for example those disclosed in PCT applications WO 96/31792 and WO 97/49740 which are herewith incorporated by reference.
The material to be coated may also be any blood-contacting material conventionally used for the manufacture of renal dialysis membranes, blood storage bags, pacemaker leads or vascular grafts. For example, the material to be modified on its surface may be a polyurethane, polydimethylsiloxane, polytetrafluoroethylene, polyvinylchloride, Dacron(trademark) or a composite made therefrom.
Moreover, the material to be coated may also be an inorganic or metallic base material with or without suitable reactive groups, e.g. ceramic, quartz, or metals, such as silicon or gold, or other polymeric or non-polymeric substrates. E.g. for implantable biomedical applications, ceramics or carbohydrate containing materials such as polysaccharides are very useful. In addition, e.g. for biosensor purposes, dextran coated base materials are expected to reduce nonspecific binding effects if the structure of the coating is well controlled. Biosensors may require polysaccharides on gold, quartz, or other non-polymeric substrates.
The form of the material to be coated may vary within wide limits. Examples are particles, granules, capsules, fibres, tubes, films or membranes, preferably moldings of all kinds such as ophthalmic moldings, in particular contact lenses.
According to step (b) of the invention, one or more different hydrophilic telomers of formula (1) are covalently bound to the surface of the material to be modified on its surface, for example, via reaction of a functional group of the material surface with the group T of the telomer of formula (1).
Suitable functional groups may be inherently (a priori) present at the surface of the material to be modified on its surface. If substrates contain too few or no reactive groups, the material surface can be modified by methods known per se, for example plasma chemical methods (see, for example, WO 94/06485 or WO 98/28026), or conventional functionalization with groups such as xe2x80x94OH, xe2x80x94NH2 or xe2x80x94CO2H produced. Suitable functional groups may be selected from a wide variety of groups well known to the skilled artisan. Typical examples are e.g. hydroxy groups, amino groups, carboxy groups, carbonyl groups, aldehyde groups, sulfonic acid groups, sulfonyl chloride groups, isocyanato groups, carboxy anhydride groups, lactone groups, azlactone groups, epoxy groups and groups being replaceable by amino or hydroxy groups, such as halo groups, or mixtures thereof. Preferred functional groups on the material surface are amino, carboxy, carboxy anhydride, lactone, azlactone or isocyanato groups, in particular amino, carboxy anhydride, epoxy, azlactone or isocyanato groups.
A preferred method for attaching reactive groups to the material surface comprises the plasma induced polymerization of an ethylenically unsaturated compound carrying a reactive group on the material surface according to the method as described in WO 98/28026. Suitable ethylenically unsaturated monomers which may be used in this process are any polymerizable unsaturated compound which carries reactive groups and can be evaporated and introduced into a plasma generating apparatus to contact the material to be coated provided therein. Examples of reactive groups to be contemplated herein include isocyanate (xe2x80x94NCO), isothiocyanate (xe2x80x94NCS), epoxy, anhydride, azlactone and lactone (e.g. xcex2-, xcex3-, xcex4-lactone) groups. Specific examples of preferred ethylenically unsaturated compounds carrying reactive groups are 2-isocyanatoethyl-methacrylate (IEM), glycidyl methacrylate, (meth)acrylic acid anhydride and 4-vinyl-2,2-dimethylazlactone.
One preferred embodiment of step (b) of the process of the invention comprises providing an amino or hydroxy group modified material surface and reacting said amino or hydroxy groups with a hydrophilic telomer of formula (1), wherein T is carboxy or a carboxy derivative. Another preferred embodiment of step (b) of the process of the invention comprises providing a material surface comprising carboxy, carboxy anhydride, lactone, azlactone or isocyanato groups and reacting said reactive groups with a hydrophilic telomer of formula (1), wherein T is amino.
The reactions of the reactive groups on the material surface to be coated with the hydrophilic telomer of formula (1) are well-known in the art and may be carried out as desribed in textbooks of organic chemistry. For example, in case that the material surface to be coated has been previously modified to carry isocyanato groups, the reaction of the isocyanato groups with a compound of formula (1) wherein T is an hydroxy or amino group may be carried out in an inert organic solvent such as acetonitrile, an optionally halogenated hydrocarbon, for example petroleum ether, methylcyclohexane, toluene, chloroform, methylene chloride and the like, or an ether, for example diethyl ether, tetrahydrofurane, dioxane, or a more polar solvent such as DMSO, DMA, N-methylpyrrolidone, at a temperature of from 0 to 100xc2x0 C., preferably from 0 to 50xc2x0 C. and particularly preferably at room temperature, optionally in the presence of a catalyst, for example a tertiary amine such as triethylamine or tri-n-butylamine, 1,4-diazabicyclooctane, or a tin compound such as dibutyltin dilaurate or tin dioctanoate. In addition, the reaction of the isocyanato groups of the primary coating with a compound of formula (3) wherein X is an amino group also may be carried out in an aqueous solution in the absence of a catalyst. It can be advantageous to carry out the above reactions under an inert atmosphere, for example under an nitrogen or argon atmosphere.
In case that the material surface to be coated has been previously modified to carry azlactone groups, the reaction of the azlactone groups with a compound of formula (1) wherein T is an amino or hydroxy group, may be carried out at room temperature or at elevated temperature, for example at about 20 to 75xc2x0 C., in water, in a suitable organic solvent or mixtures thereof, for example in an aqueous medium or in an aprotic polar solvent such as DMF, DMSO, dioxane, acetonitrile and the like.
In case that the material surface to be coated has been previously modified to carry epoxy groups, the reaction of the epoxy groups with a compound of formula (1) wherein T is an amino group may be carried out, for example, at room temperature or at elevated temperature, for example at about 20 to 100xc2x0 C., in water, in a suitable organic solvent or in mixtures thereof.
In case that the material surface to be coated has been previously modified to carry epoxy groups, the reaction of the epoxy groups with a compound of formula (1) wherein T is a hydroxy group may be carried out, for example, at room temperature or at elevated temperature, for example at about 20 to 100xc2x0 C., in an aprotic medium using a base catalyst, for example Al(Oxe2x80x94C1-C6-alkyl)3 or Ti(Oxe2x80x94C1-C6-alkyl)3. The same applies to the reaction of a hydroxy group modified surface with a compound of formula (1) wherein T is an epoxy group.
In case that the material surface to be coated has been previously modified to carry carboxy anhydride groups, the reaction of the carboxy anhydride with a compound of formula (1) wherein T is an amino or hydroxy group may be carried out as described in organic textbooks, for example in an aprotic solvent, for example one of the above-mentioned aprotic solvents, at a temperature from room temperature to about 100xc2x0 C.
In case that the material surface to be coated has been previously modified to carry carboxy groups, the reaction of the carboxy groups with the hydroxy, amino or epoxy groups T of a compound of formula (1), or the reaction of an amino or hydroxy group modified surface with a compound of formula (1), wherein T is carboxy, may be carried out under the conditions that are customary for ester or amide formation, for example in an aprotic medium at a temperature from about room temperature to about 100xc2x0 C. It is further preferred to carry out the esterification or amidation reaction in the presence of an activating agent, for example N-ethyl-Nxe2x80x2-(3-dimethyl aminopropyl)carbodiimide (EDC), N-hydroxy succinimide (NHS) or N,Nxe2x80x2-dicyclohexyl carbodiimide (DCC).
The coated material obtained according to the invention may be purified afterwards in a manner known per se, for example by washing or extraction with a suitable solvent such as water.
According to the process of the invention, the material surface to be modified is provided with a coating having a so-called bottle brush-type structure (BBT) composed of tethered xe2x80x9chairyxe2x80x9d chains. The BBT structure of the coatings of the invention may be varied within wide limits, for example, by a suitable choice of the hydrophilic telomer of formula (1). Such BBT structures in one embodiment comprise a long hydrophilic or hydrophobic backbone which carries relatively densely packed comparatively short hydrophilic side chains (called primary bottle brushes). Another embodiment relates to secondary bottle brushes which are characterized in that the hydrophilic side chains themselves carry densely packed hydrophilic xe2x80x9csecondaryxe2x80x9d side chains. Polymeric coatings of said primary and secondary BBT structures to a certain extent mimic highly water-retaining structures occurring in the human body, for example in cartilage or mucosal tissue.
The coating thickness of the coated material surfaces obtained according to the process of the invention depends principally on the desired properties. It can be, for example, from 0.001 to 1000 xcexcm, preferably from 0.005 to 100 xcexcm, more preferably from 0.01 to 50 xcexcm, even more preferably from 0.01 to 5 xcexcm, especially preferably from 0.01 to 1 xcexcm and particularly preferably from 0.01 to 0.5 xcexcm.
A further embodiment of the invention relates to a material that is coated by the process of the invention.
The material that is coated by the process of the invention is, for example, an organic bulk material, preferably a biomedical device, e.g. an ophthalmic device, preferably a contact lens including both hard and particularly soft contact lenses, an intraocular lens or artificial cornea. Further examples are materials useful for example as wound healing dressings, eye bandages, materials for the sustained release of an active compound such as a drug delivery patch, moldings that can be used in surgery, such as heart valves, vascular grafts, catheters, artificial organs, encapsulated biologic implants, e.g. pancreatic islets, materials for prostheses such as bone substitutes, or moldings for diagnostics, membranes or biomedical instruments or apparatus.
The biomedical devices, e.g. ophthalmic devices obtained according to the invention have a variety of unexpected advantages over those of the prior art which make those devices very suitable for practical purposes,e.g. as contact lens for extended wear or intraocular lens. For example, they do have a high surface wettability which can be demonstrated by their contact angles, their water retention and their water-film break up time or pre-lens or on-eye tear film break up time (TBUT).
The TBUT plays an particularly important role in the field of ophthalmic devices such as contact lenses. Thus the facile movement of an eyelid over a contact lens has proven important for the comfort of the wearer; this sliding motion is facilitated by the presence of a continuous layer of tear fluid on the contact lens, a layer which lubricates the tissue/lens interface. However, clinical tests have shown that currently available contact lenses partially dry out between blinks, thus increasing friction between eyelid and the lens. The increased friction results in soreness of the eyes and reduced movement of the contact lenses. Now it has become feasible to considerably increase the TBUT of commercial contact lenses such as, for example, Focus Dailies(trademark), Focus New Vues(copyright) or Lotrafilcon A lenses, by applying a surface coating according to the invention. On the base curve of a contact lens, the pronounced lubricity of the coating facilitates the on-eye lens movement which is essential for extended wear of contact lenses. Moreover, the materials obtained by the process of the invention provide additional effects being essential for lenses for extended wear, such as an increased thickness of the pre-lens tear film which contributes substantially to low microbial adhesion and resistance to deposit formation. Due to the extremely soft and lubricious character of the novel surface coatings, biomedical articles such as in particular contact lenses coated by the process of the invention show a superior wearing comfort including improvements with respect to late day dryness and long term (overnight) wear. The novel surface coatings moreover interact in a reversible manner with occular mucus which contributes to the improved wearing comfort.
In addition, biomedical devices, e.g. ophthalmic devices such as contact lenses, coated by the process of the invention, have a very pronounced biocompatibility combined with good mechanical properties. For example, the devices are blood compatible and have a good tissue integration. In addition, there are generally no adverse eye effects observed, while the adsorption of proteins or lipids is low, also the salt deposit formation is lower than with conventional contact lenses. Generally, there is low fouling, low microbial adhesion and low bioerosion while good mechanical properties can be for example found in a low friction coefficient and low abrasion properties. Moreover, the dimensional stability of the materials obtained according to the invention is excellent. In addition, the attachment of a hydrophilic surface coating at a given bulk material according to the invention does not affect its visual transparency.
In summary, the ophthalmic devices obtained by the process of the invention, such as contact lenses and artificial cornea, provide a combination of low spoilation with respect to cell debris, cosmetics, dust or dirt, solvent vapors or chemicals, with a high comfort for the patient wearing such opthalmic devices in view of the soft hydrogel surface which for example provides a very good on-eye movement of the ohthalmic device.
Biomedical devices such as renal dialysis membranes, blood storage bags, pacemaker leads or vascular grafts coated by the process of the invention resist fouling by proteins by virtue of the continuous layer of bound water, thus reducing the rate and extent of thrombosis. Blood-contacting devices fabricated according to the present invention are therefore haemocompatible and biocompatible.
In the examples, if not indicated otherwise, amounts are amounts by weight, temperatures are given in degrees Celsius. Tear break-up time values in general relate to the pre-lens tear film non-invasive break-up time (PLTF-NIBUT) that is determined following the procedure published by M. Guillon et al., Ophthal. Physiol. Opt. 9, 355-359 (1989) or M. Guillon et al., Optometry and Vision Science 74, 273-279 (1997). Average advancing and receding water contact angles of coated and non-coated lenses are determined with the dynamic Wilhelmy method using a Krxc3xcss K-12 instrument (Kruss GmbH, Hamburg, Germany). Wetting force on the solid is measured as the solid is immersed in or withdrawn from a liquid of known surface tension.
Preparation of Functionalized Contact Lens Surfaces